Acute and chronic angiotensin hypertension: neural and non-neural
components, time course, and dose-dependency.
Li, Qian, William E. Dale, Eileen M. Hasser, and Edward H. Blaine.
From the Dalton Cardiovascular Research Center and the Departments
of Physiology, Pharmacology and Veterinary Biomedical Sciences,
University of Missouri, Columbia, Missouri 65211
APStracts 3:0096R, 1996.
We examined the mechanisms mediating hypertension in conscious rats
during acute and chronic infusion of angiotensin II (Ang II) at
pressor doses (50, 100 and 200 ng/kg/min). Trimethaphan-induced blood
pressure reduction was inversely related to the acute dose of Ang II,
consistent with a constrictor action of Ang II on vascular smooth
muscle and withdrawal of sympathetic tone. During chronic Ang II
infusion, the entire increase in mean arterial pressure (MAP) was
inhibited by trimethaphan, consistent with neural mediation. During
acute Ang II hypertension, the AT1-specific receptor blocker losartan
induced a large fall in MAP (64"4 mm Hg) in ganglion-blocked
(chlorisondamine) rats, while during chronic Ang II hypertension,
losartan had only a small hypotensive effect (11"3 mm Hg). To
determine the time course of the change from vascular smooth muscle
action to neural action, we measured MAP in response to trimethaphan
during the first 24 hours of Ang II infusion. After 5 h, the minimal
MAP in response to trimethaphan was significantly higher than that
before Ang II. Following 10 h of infusion, trimethaphan decreased MAP
to pre-Ang II levels. That is, the neural component was fully active
after only 10 h of infusion in rats. Finally, chronic administration
of Ang II resulted in a dose-related increase in MAP which, at all
doses, was completely inhibited by trimethaphan. These findings are
consistent with Ang II acting primarily on vascular smooth muscle
during acute infusion and via neural pathways during chronic
treatment. The transition from direct smooth muscle to indirect
neural action is rapid in rats (<10 h) and the MAP and neural
responses to Ang II are dose-related during chronic hypertension.
Received 7 July 1995; accepted in final form 6 March 1995.
APS Manuscript Number R427-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96